The present invention relates to the field of ophthalmic surgery, and in particular to intraocular procedures which facilitate cataract removal. Basically, the invention concerns treating the cataractous lens by introducing a lenticular tissue dispersing agent through a small opening in the lens capsule so that the lens capsule remains substantially intact. The tissue dispersing agent, which is preferably a hydrolytic enzyme capable of disrupting cellular adhesion in the lenticular tissue, is effectively contained in the lens by the use of a gel-forming substance which functions to block the opening in the lens capsule, preventing escape of the enzyme. Enzymatic dispersion of the lenticular tissue may be used to particular advantage in combination with a non-invasive technique for fragmenting the lens tissue, preferably, laser-induced phacofracture.
A cataractous eye is one in which an opacity develops that interferes with the normal transmission of light to the retina, thereby causing diminished vision. Although there are several types of fluids and tissues within the eye which may become opaque and cause a cataract, the vast majority of cataracts are associated with a clouding of the lenticular or lens tissue. These changes are irreversible and the only known remedy for the resultant blindness is surgical removal of the opaque lens tissue.
The lens of the eye is composed of several highly integrated structural components. The nucleus, which occupies about 60-75% of the lens volume, is composed of collapsed and layered cells which have lost virtually all intracellular organelles. The structure of the nucleus can be considered a lamellar assembly of membranes, comparable to the layers of an onion. Surrounding the nucleus is the cortex, which is generally soft and contains cells undergoing differentiation and elongation into nuclear cells. The exterior part of the cortex includes the highly proliferating epithelial cells contiguous to the lens capsule. Enveloping the lens itself, like an onion skin, is the transparent capsule, which is a structural protein complex whose composition is related to basal membrane collagen. Attached to the lateral, circular edge of the capsule and embedded within it are microscopic, suspensory tendrils called zonules. The zonules, in turn, are connected to the ciliary body of the eye which contains contractile tissue. Lens accommodation occurs by contraction or relaxation of the ciliary body. The resulting mechanical force is transmitted to the periphery of the lens capsule via the zonules. The radial tension at the capsule causes the ordinarily soft lens to flatten or upon reduction of tension to assume a more bulbous shape. Therefore conformational adaptation of the lens is the basis of refractive accommodation and hence the ability to focus on objects far or near.
For many years, the surgical procedure of choice for removal of cataracts was intracapsular extraction, in which the entire lens with its capsule is removed after disruption of the zonular attachment. An undesirable consequence of this procedure, however, is the removal of the physical partition separating the anterior segment aqueous fluid from the posterior segment vitreous fluid. Furthermore, the resulting aphakic (lensless) eye requires extraocular optical devices, such as thick eye glasses or contact lenses to compensate for loss of visual acuity.
More recently, the successful introduction of the intraocular lens (IOL) implant has substantially obviated postoperative optical correction and is now routinely practiced. The surgical procedure employed for cataractous lens removal in conjunction with IOL implants is known as extracapsular extraction. This procedure involves rupturing the anterior lens capsule, prolapsing the lens from the remaining capsular tissue into the anterior chamber and expressing it through a relatively large limbal incision. The primary difference between the intracapsular and extracapsular procedures is that in the latter, the posterior capsule is left intact. The posterior capsule maintains a natural barrier between the posterior and anterior segments of the eye, and together with the iris, physically supports the IOL within the lenticular region.
A requirement of the extracapsular procedure, is that the remaining capsular structure be carefully cleaned of adhering epithelial cells, which, if not removed, may later proliferate causing an opacity to develope, known as Elschnig's pearls. Although laser energy has reportedly been used to effect preoperative fracture of the opacified lens in cataract surgery, this phacofracture technique is not entirely satisfactory for extracapsular extractions. The laser-induced phacofracture technique described by Chambless, 11 Am. Intra-ocular Implant Soc. J. 33-34 (1985), for example, while effective in disrupting compact tissue, is relatively ineffective on softer cortical tissue. Cortical tissue is moderately elastic and difficult to mechanically disperse with the laser technique. Also, close proximity to the capsule precludes safe use of laser-induced phacofracture techniques on the cortex due to short range secondary effects of laser-induced cavitation which are largely uncontrollable. Therefore, the tissue fracture must be induced sufficiently interior to the capsular boundary to prevent cavitation damage to the lens capsule. For these reasons, the use of phacofracture alone has little practical effect on dispersion and removal of distal epithelial cells.
Even with the remarkable advances in the microsurgical techniques presently employed in intralenticular cataract surgery, the operation has been unable to yield an improved therapeutic result for the patient, in that removal of the opacified lens tissue results in loss of the adaptive focusing or accommodation of the eye. Presently, there is no post-operative prosthesis that can restore the accommodative function of the eye.
An accommodative lens prosthesis would require, by today's surgical procedure, reconstruction of the lens capsule and contents and reattachment to the zonular elements. Such reconstructive surgery is an impossible task with available or even contemplated technology. A conceptually simpler approach would be to leave the native lens capsule and related, contractile structures in place after surgical removal of the opaque tissue. Ideally removal would include nucleus, cortex and epithelial cells, the latter to prevent unorganized regrowth of lens tissue ultimately leading to opacification of the evacuated capsule. In order for this approach to succeed, a procedure must be provided for removing the highly integrated intracapsular tissue, yet maintaining the integrity of the capsule. Once thoroughly evacuated, the clear capsule could conceivably be refilled with a soft gel-like substance possessing an appropriate refractive index that could function like a native lens.
Evacuation of the lens tissue from within the lens capsule requires physical transfer of the contents across the capsular boundary. The most expedient and probably the most realistic approach would be to transform the intracapsular tissue into a liquid state which could be aspirated through a small diameter cannula penetrating the capsule. The more homogenous and fluid-like the contents become, the smaller the cannular dimension and the less trauma to the capsule. Likewise, in refilling the evacuated capsule, the smaller the hole in the capsule, the easier it will be to contain the injected fluid until in situ cross-linking or polymerization can occur to produce a flexible lens prosthesis.
Endocapsular removal of lens tissue and refilling of the evacuated capsule have been reported by Kessler, 7 Annals of Opthal. 1059-62 (1975), and more recently by Schanzlin et al., 12 Cataract, May, pp 11-14 (1985). Although the eye from which the lens was reportedly removed appeared to conditionally accommodate the prosthesis post-operatively, these procedures are generally unsatisfactory for practical application. It is questionable whether the micromechanical advancement in ophthalmic surgery alone will ever enable endocapsular removal of lens tissue in a manner which allows in situ reconstruction of an accommodative lens prosthesis. As noted above, what is needed is a procedure whereby the lens tissue within the capsule is fragmented, liquified or otherwise dispersed into a physical state allowing complete evacuation through a very small opening in the capsule.
Experimental in vitro softening of lens tissue employing proteolytic enzymes was reported as early as 1969 by Bonnet and Trouche, 69 Bulletin des Societes d' Ophtolmolgic de France 583-86 (1969). Subsequently Spina and Weibel developed a lenticular injection procedure which successfully contained injected lens digesting enzymes within the lens tissue, which is the subject of U.S. Pat. No. 4,078,564. Enzymatic dispersion of the lenticular tissue in this way is practicable because the lens capsule actually isolates the lens to such an extent that exogenous enzyme may be safely introduced into the lens without creating an immunologic foreign protein response thereto. This procedure was later refined for the removal of cataractous tissue in vivo by introducing highly specific tissue dispersing proteinases that reduce lens tissue to an aspiratible state, but do not digest the capsule. The latter procedure is the subject of U.S. Pat. No. 4,191,176, also granted to Spina and Weibel. It was believed that such a procedure would allow easier removal of lens tissue using atraumatic techniques such as simple aspiration in situ or after manipulation into the anterior chamber.
However, in experiments on senile cataracts, it has been found that this procedure is not satisfactory in penetrating hard nuclear tissue. These experiments have shown that injection of enzyme is largely confined to the cortex. The nucleus with its compact structure is dispersed by diffusion of the proteinase, achieving only slow, peripheral sloughing of nuclear cells. Due to inherent auto-inactivation mechanisms of the proteinase, the enzyme may be substantially deactivated before the nucleus is fully dispersed into an aspiratible state. A nucleus which is substantially reduced in size but remains a coherent tissue mass is not a problem in the conventional extracapsular procedure. The remaining lens is ultrasonically emulsified after prolapsing into the anterior chamber or simply expressed through the limbal incision. The presence of remaining coherent tissues, however, cannot be tolerated in endocapsular evacuation through a microcannula.
In order to effectively treat the sclerotic nuclear cataract it is important that the injected volume of the liquid dispersing agent be contained within the lens capsule and maintained in contact with the lenticular tissue. As previously mentioned, the tissue of the nucleus is not readily permeated by the treating agent and the injected fluid tends to form a fracture plane which ultimately produces a pocket within the tissue. This leads to a pocket of high, localized hydraulic pressure in the vicinity of the injection. Upon withdrawal of the microcannula the internal pressure is released by egress of the injected fluid back through the cannula track into the anterior chamber. It is important that the dispersive agent be retained within the lenticular region in order that it can act upon the target tissue. Furthermore, it is necessary to contain all of the injected agent in the lens to provide a consistent and predictable dose-related result.
In connection with our earlier enzymatic lens digestion procedure it was discovered that introduction of a small air bubble into the opening on the lens capsule through which the enzyme is delivered is an effective way of sealing the opening to prevent escape of the enzyme from the relatively soft lens of the test subject. This concept and related enzyme delivery devices are described in Spina and Weibel, U.S. Pat. No. 4,135,516, entitled "Delivery Apparatus and Method for Treatment of Intralenticular Cataracts With Exogenous Enzymes". This approach, however, has been found to be somewhat erratic in practice where the nuclear and cortical regions of the lens are extremely dense, or pressurized vaccuoles resulting from laser-induced cavitation are present. In general the pneumatic drive assembly which forces the contents of the microannula into the lens requires excessive volumetric compression for injection into the nucleus of the hard lens. Upon release of the dispersive agent, an uncontrolled surge of air into the injected lens can occur. This pneumatic surge may cause rupture of the lens capsule, escape of the delivered fluid about the cannula or other complications.
Against this background, it will be appreciated that an effective surgical procedure for completely removing the highly integrated cataractous tissue from the lens capsule, so as to allow refilling of the capsule with a material capable of restoring accommodative function of the eye, remains a highly desirable objective.